1H and 13C NMR of synthetic steroid sapogenins. Part II. C-23 Substituted derivatives of (25S)-spirostanes

Abstract

The main 1 H and 13 C NMR characteristics of synthetic (25S)-5β-spirostantes are described. Changes on chemical shifts due to substitution at C-23 are briefly analyzed.

Smilagenin Transformation Products Under Lewis Acid Catalysis in Acetic Anhydride and Synthesis of 23-Acetyl-Spirostanols

“…Smilagenin ( 4 ) and 23-acetyl-smilagenin ( 14 ) show a triplet and a doublet of doublet with similar chemical shifts for H-26, typical of equatorial methyls at C-25. However, the same protons show a drastic difference in chemical shifts in sarsasapogenin 2 and 23-acetyl-sarsasapogenin 15 with an axial methyl group at C-25 10,17 (Figure 4). This allows to establish that 14 and 15 have the methyl group at C-25 oriented in equatorial and axial position, respectively.…”

“…Having the two C-20 isomeric epoxycholestene derivatives of smilagenin, we decided to explore their reactivity under basic conditions to give stereoisomeric 23-acetyl-spirostanols. Thus, treatment of the mixture as well as each of the epimeric epoxycholestenes 6 and 9 with KOH/EtOH at room temperature 7 c ,10 proceeded with high stereospecificity to give two diastereomeric 23-acetyl-spirostanols ( 14 and 15 ) (Scheme 2). The structures of these compounds were determined by NMR, and the configuration at C-20, C-22, C-23, and C-25 for compound 15 was established by X-ray crystal analysis as 20 R , 22 R , 23 S , and 25 R .…”

“…The 13 C chemical shifts for isomeric spirostanols 14 and 15 show no significant differences for compounds with different configuration and were assigned by comparison with literature data and 2D experiments. 7 c ,10,11 a,j…”

“…Structural data of steroidal sarsasapogenin acetate ( 16), smilagenin ( 4), (20R,22R,23S,25R)-23-acetyl-5β-spirostan-3β-ol (15), and 23-acetyl-sarsasapogenin (17) 10 were collected on an Enraf Nonius KappaCCD at 293 K with MoKα radiation (λ = 0.7173 Å). The crystals were mounted on conventional MicroLoops TM .…”

“…The organic phase was extracted with ethyl acetate, neutralized with a saturated sodium bicarbonate solution, dried with anhydrous Na 2 SO 4 , and evaporated to dryness under vacuum. The crude product was chromatographed over silica gel using hexane/EtOAc (85:15) to give 0.65 g of a mixture of 6 and 9 (R f = 0.6, 70% yield in a 9:1 ratio, as determined by HPLC), 20% of (E)-(20S,25R)-20,23-Diacetyl-5β-furost-22-ene-3β,26diyl diacetate ( 7 1), 206 (38), 205 (100), 191 (30), 179 (21), 166 (24), 129 (20), 111 (10), 97 (16), 83 (18), 55 (25), 43 (41); 1 H NMR (500 MHz, CDCl 3 ) δ: 5.11 (1H, td, J = 7.8 Hz, J = 3.0 Hz, H-16), 5.05 (1H, br s, H-3), 4.05 (1H, dq, J = 11.0, 6.9 Hz, H-20), 3.99 (1H, ddd, J = 10.1, 3.4, 2.0 H-26eq), 3.45 (1H, t, J = 10.1 Hz, H-26ax), 2.20 (3H, s, 23-COCH 3 ), 2.04 (3H, s, 3-OAc), 1.84 (3H, s, 16-OAc), 1.17 (3H, d, J = 6.9 Hz, CH 3 -21), 0.97 (3H, d, J = 7.7 Hz, CH 3 -27), 0.98 (3H, s, CH 3 -19), 0.89 (3H, s, CH 3 -18); 13 -12), 39.9 (C-9), 37.2 (C-5), , 25.9 (C-7), 24.9 (C-2), (6), 107 (14), 42 (49); 1 H NMR (400 MHz, CDCl 3 ) δ: 5.06 (1H, br s, H-3), 4.99 (1H, ddd, J = 7.6, 4.3 Hz H-16) 3.64 (1H, q, J = 7.0 Hz, H-20), 3.42 (2H, m, H-26), 2.43 (dd, 1H, J = 14, 8 Hz, H-24), 2.25 (3H, s, 23-COCH 3 ), 2.04 (3H, s, 3-OAc), 1.18 (3H, d, J = 7.3 Hz, CH 3 -21), 1.00 (3H, d, J = 6.9 Hz, CH 3 -27), 0.97 (3H, s, CH 3 -19), 0.56 (3H, s, CH 3 -18); 13 (20R,25R)-23-Acetyl-22,26-epoxy-5β-cholest-22-ene-3β,16β-diyl diacetate (9) Lacquer and used in the next step for obtaining of the spirostanol. MS, m/z (%): 542 ([M + ] 0.9), 467 (3), 255 (6), 205 (100), 191 (30), 166 (28) 43 (88); 1 H NMR (400 MHz, CDCl 3 ) δ: 5.05 (1H, td, J = 7.5 Hz, J = 4.2 Hz, H-16), 4.98 (1H, br s, H-3), 4.06-3.93 (m, 2H H-20, H-26eq), 3.35 (1H, t, J = 9.5 Hz, H-26ax), 2.49 (2H, dd, H-24),2.22 (3H, s, 23-COCH 3 ), 2.02 (3H, s, 3-OAc), 1.96 (3H, s, 16-OAc), 0.97 (3H, d, J = 6.9 Hz, CH 3 -21), 0.97 (3H, d, J = 6.2 Hz, CH 3 -27), 0.92 (3H, s, CH 3 -19), 0.73 (3H, s, CH 3 -18); 13…”